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Biomedical subjects

M Schrappe

Publications and source records attributed to M Schrappe.

At least 127 records · Page 7Linked to original sources
PubMed1996

Genetic evidence for latent Septata intestinalis infection in human immunodeficiency virus-infected patients with intestinal microsporidiosis.

Sequence data of the small subunit rRNA (SSU-rRNA) gene were used to identify Septata intestinalis in biopsies of human immunodeficiency virus-infected patients by polymerase chain reaction (PCR), southern blot hybridization, cloning, and comparative genetic sequencing. DNA products of correct size could be amplified from all examined tissues with S. intestinalis infection but also from 2 biopsies with Enterocytozoon bieneusi and from 1 biopsy with Encephalitozoon cuniculi infection. Southern blot hybridization with an S. intestinalis-specific probe and partial sequencing of the DNA fragments showed high homology with published S. intestinalis sequences and confirmed that the amplified PCR products really derived from the SSU-rRNA gene of S. intestinalis. PCR testing can detect very light infections with S. intestinalis. Thus, S. intestinalis seems to occur more frequently in the form of latent infections and the true prevalence of the parasites may be much higher than previously reported.

Animals↗
PubMed1996

Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. Berlin-Frankfurt-Münster Relapse Study Group.

PURPOSE: In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute peripheral blast count (PBC) at the time of relapse on the response to salvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis. PATIENTS AND METHODS: Since 1983, 260 children with a first isolated BM relapse of ALL that occurred 6 months or later after elective cessation of front-line therapy were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt-Münster (BFM) Relapse Study Group. All patients received intensive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of subclinical meningeal leukemia consisted of high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988. RESULTS: At the time relapse was diagnosed, PBC varied considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL). Achievement of a second complete remission (CR) was not significantly different in children without detectable circulating blasts at relapse (37 of 38) and those with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51 children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015). At a median follow-up time of 40 months, the 10-year event-free survival (EFS) probability was significantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating blasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission > or = 48 months was an additional independent indicator of adverse prognosis, while preventive cranial irradiation improved outcome independently of PBC. CONCLUSION: The absence of blasts on peripheral-blood smears at the time of a first late isolated BM relapse of childhood ALL is associated with a favorable response and prognosis in chemotherapy-treated children, who should be regarded as ineligible for bone marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response.

Adolescent↗
PubMed1996

Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05-92.

A variety of oncogenes are activated by specific chromosomal translocations, which are associated with distinct subtypes of leukemia. The identification of these rearrangements provides critical diagnostic and prognostic information, which may contribute to the selection of specific anti-leukemic therapy. The translocation t(9;22), the equivalent of the BCR/ABL rearrangement, is associated with a poor prognosis. We therefore used RT-PCR to detect this molecular event in a prospective study including 890 children. 673 of them suffered from acute lymphoblastic leukemia (ALL) at primary diagnosis and a transcription of the chimeric gene was detected in 21 of 648 with a successful analysis (3.2%). All children were treated by one of the two German multicenter childhood ALL therapy studies ALL-BFM-90 or COALL-05-92, respectively. Comparison of clinical features between BCR/ABL-positive and -negative children showed no significant differences regarding WBC, percentage of blasts, splenomegaly, hepatomegaly and age. Immunophenotypic studies at diagnosis in 21 BCR/ABL-positive children identified common ALL in 16 patients (76.2%), pre-B-ALL in four (19.0%), and an early T-lineage ALL in one (4.8%). Coexpression of myeloid antigens (CD13 and/or CD33) was observed in six of 16 common ALL patients as well as in the one child with early T-lineage ALL phenotype. The type of breakpoint (m-BCR/ABL: n = 14; M-BCR/ABL: n = 7) showed no correlation with clinical parameters. A comparison of cytogenetic and molecular data was performed in 16 positive patients and was concordant in all of them. We analyzed the response to the prednisone pretreatment and found a higher incidence of poor responders among the BCR/ABL-positive children. Regarding the event-free survival (EFS) of BCR/ABL-positive (0.53) and -negative patients (0.79) after a follow-up of 2 years, significant differences (P < 0.05) between both groups could be demonstrated.

Adolescent↗
PubMed1995

A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma.

9 patients with stage IV neuroblastoma were treated with 19 courses of human/mouse chimeric monoclonal antiganglioside GD2 antibody ch14.18 at dose levels of 30, 40 and 50 mg/m2/day for 5 days per course. The maximum tolerated dose (MTD) per injection was 50 mg/m2/day. 7 patients received more than one course of treatment, and none revealed any human anti-mouse antibody (HAMA) response. Clinical side-effects of patients treated with ch14.18 were abdominal and joint pains, pruritus and urticaria. One patient presented with a transient pupillatonia, while 2 others showed a unilateral atrophy of the optical nerve that was probably attributable to prior therapies. A complete remission was seen in 2 patients, partial remission in 2 patients, a minor response in 1 patient and stable disease in 1 patient. 3 patients showed tumour progression. Thus, our results indicate that treatment with chimeric MAb ch14.18 can elicit some complete and partial tumour responses in neuroblastoma patients.

3-Iodobenzylguanidine↗
PubMed1995

Intestinal microsporidiosis with Septata intestinalis in a patient with AIDS--response to albendazole.

Microsporidiosis is a common finding in HIV-infected patients who have diarrhoea. The species most commonly causing gastrointestinal disease is Enterocytozoon bieneusi. Recently Septata intestinalis has been described as a cause of diarrhoea and disseminated infection in patients with AIDS. A 44-year-old homosexual man with severe immunodeficiency (CD4 cell count 40/microliters) had a history of watery diarrhoea for 2 weeks. Microsporidian spores measuring 1.2 to 1.5 x 2.5 to 3.0 microns were found in stool samples. Electron microscopy of duodenal biopsies confirmed the diagnosis of intestinal microsporidiosis and showed parasitophorous vacuoles with the typical ultrastructure of S. intestinalis. The patient was treated with albendazole (400 mg twice daily) and became asymptomatic within 4 days. No spores could be detected in stool samples after a treatment period of 14 days. About 25 infections with S. intestinalis have been reported to date, and the case presented here is the first in a German patient.

AIDS-Related Opportunistic Infections↗
PubMed1995

Stimulated duodenal/bile juice aspiration for diagnosis of enteric pathogens in HIV-infected patients.

Gastrointestinal and biliary abnormalities are common in the acquired immunodeficiency syndrome. Although obviously related to opportunistic infections in many cases, often no infectious agent can be identified. The specific diagnosis depends on invasive methods such as endoscopic retrograde cholangiography and liver histology. To evaluate an alternative and less invasive first-line approach, we conducted a prospective study of microscopic examination of aspirated duodenal/bile juice, to try to identify microbial causes of human immunodeficiency virus (HIV)-related gastrointestinal and biliary tract disease. Sixty-four HIV-infected patients underwent upper gastrointestinal endoscopy with biopsies from the esophagus, stomach, and duodenum, and aspiration of stimulated duodenal/bile juice. Biopsies, duodenal/bile juice, and stool samples were examined for enteric pathogens. Twenty-seven intestinal infections were found in 22 of the 64 patients (34%), 12 (44%) of which were diagnosed by duodenal/bile juice examination. Seven of the 27 infections (26%) were diagnosed exclusively in duodenal/bile juice, whereas 5 were found in biopsies or stool samples as well. Twenty infections (74%) were demonstrated in intestinal biopsies and/or stool samples, 15 without any positive result in duodenal/bile juice. The proportion of patients with elevated alkaline-phosphatase and gamma-glutamyl-transpeptidase activities was higher in patients with infectious agents detected in duodenal/bile juice (5 of 11, 45%), than in patients with infectious agents found exclusively in intestinal biopsies and/or stool samples (2 of 11, 18%). Analysis of duodenal/bile juice is a simple, rapid, and effective method for the detection of enteral pathogens in HIV-related gastrointestinal and biliary dysfunction. It increases the diagnostic yield above the results of intestinal biopsies and stool examinations alone.

Adult↗
PubMed1995

Detection of microsporidia (Enterocytozoon bieneusi) in intestinal biopsy specimens from human immunodeficiency virus-infected patients by PCR.

Intestinal microsporidiosis has been implicated as a major cause of chronic diarrhea in human immunodeficiency virus (HIV)-infected patients. So far diagnosis depends on direct visualization of the parasites by light and transmission electron microscopy. We evaluated the diagnostic value of microsporidian DNA amplification by PCR on duodenal biopsy specimens obtained from patients with and without intestinal microsporidiosis caused by Enterocytozoon bieneusi. Thirteen HIV-infected patients (all CDC stage C3) were studied. Eight patients had intestinal microsporidiosis caused by E. bieneusi (n = 6), Septata intestinalis (n = 1), and Encephalitozoon cuniculi (n = 1); microsporidioses were diagnosed by light microscopy of stool samples and confirmed by light and electron microscopy of intestinal biopsy specimens. Five patients had no microsporidia in their stool samples or in their intestinal biopsy specimens, as examined by light and electron microscopy. Additionally, DNA prepared from Toxoplasma gondii derived from mouse ascites was used as a further control. A 353-bp DNA fragment of the small-subunit rRNA gene could be amplified from all six biopsy specimens infected with E. bieneusi, and the nature of the PCR products was confirmed by Southern blot hybridization. No amplification of DNA fragments was seen by using DNA extracted from biopsy specimens with S. intestinalis or E. cuniculi infection or without microsporidian infection and with template DNA extracted from T. gondii. The results suggest that PCR testing of intestinal biopsy specimens may be a useful approach to diagnosing microsporidiosis in HIV-infected patients.

Animals↗
PubMed1995

Tissue diagnosis of intestinal microsporidiosis using a fluorescent stain with Uvitex 2B.

AIMS: To detect intestinal microsporidiosis in paraffin wax embedded biopsy specimens using a fluorescence technique incorporating optical brighteners. METHODS: Eight HIV infected patients with confirmed intestinal microsporidiosis (six with Enterocytozoon bieneusi, one with Encephalitozoon intestinalis and one with Encephalitozoon cuniculi infection) and 10 without infection were studied. Tissue sections of paraffin wax embedded duodenal biopsy specimens were stained with 1% Uvitex 2B, coded and analysed independently by two investigators. RESULTS: In all eight cases with confirmed intestinal microsporidian infection, spores could be detected easily in tissue sections using the fluorescence technique. Spores or other elements consistent with microsporidiosis were not found in the 10 patients without infection. CONCLUSION: Staining of tissue sections from paraffin wax embedded intestinal biopsy specimens with stains incorporating Uvitex 2B is a rapid and easy technique for the diagnosis of intestinal microsporidiosis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage--a report of the Berlin-Frankfurt-Münster Group.

PURPOSE: To prove the efficacy of a treatment stratified according to histology for children with non-Hodgkin's lymphoma (NHL), including acute B-cell leukemia (B-ALL). PATIENTS AND METHODS: From October 1986 to March 1990, 302 assessable patients, 0.6 to 17.8 years of age, with newly diagnosed NHL were enrolled onto study ALL/NHL-BFM 86. Fifty percent of patients had Burkitt-type lymphomas, including B-ALL; 24% had lymphoblastic lymphoma; 18% had diffuse large-cell lymphoma; and 8% had an NHL not further classified. Therapy group B included Burkitt's-type lymphomas, B-ALL, and most large-cell lymphomas including Ki-1 anaplastic large-cell lymphoma. Patients with stage I and II disease resected received three, while all others received six, 5-day therapy courses (dexamethasone, methotrexate [MTX] 0.5 g/m2 [5 g/m2 for stage IV and B-ALL], and intrathecal [IT] therapy in each course, plus ifosfamide, cytarabine, and etoposide alternating with cyclophosphamide and doxorubicin). Therapy for group non-B patients (lymphoblastic lymphoma and pleomorphic T-cell lymphoma [PTCL]) consisted of a Berlin-Frankfurt-Münster (BFM) acute lymphoblastic leukemia protocol, including cranial irradiation for advanced stage. Local therapy was restricted to patients with incomplete tumor regression. RESULTS: The probabilities of event-free survival (pEFS) at 7 years were 80% +/- 2% for the whole group, 81% +/- 3% for group B (n = 225), and 78% +/- 5% for group non-B (n = 77) with a follow-up duration of 3.6 to 7 years (median 5 years). Treatment results were comparable between NHL subtypes, except for PTCL, in which three of four patients suffered from relapse. Local disease manifestations were the most frequent site of failure. CONCLUSION: This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.

Adolescent↗
PubMed1995

Analysis of antral biopsy specimens for evidence of acquired mucosa-associated lymphoid tissue in HIV1-seropositive and HIV1-negative patients.

BACKGROUND: There is conflicting evidence concerning the prevalence of Helicobacter pylori gastritis in HIV1-infected patients. Furthermore, a possible influence of immunodeficiency on the acquisition of mucosa-associated lymphoid tissue (MALT) in the antral mucosa remains to be elucidated. METHODS: Seventy-seven consecutive HIV1-infected patients (mean age, 40.2 years) were compared in a prospective study with 77 HIV1-negative age-matched patients, using immunohistochemical stainings. RESULTS: In HIV1-infected patients the prevalence of H. pylori gastritis was lower and the inflammatory reaction less pronounced than in controls. Lymphoid follicles and intraepithelial B cells were significantly more often detected in HIV1-negative patients. CONCLUSIONS: Evidence of acquired MALT is only rarely found in HIV1-infected patients. These findings might contribute to the explanation of why low-grade gastric MALT lymphomas have not been reported in HIV1-infected patients so far.

Adult↗
PubMed1995

A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group.

OBJECTIVE: Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddI; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated. DESIGN: A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddI daily. SETTING: The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres. RESULTS: The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient). CONCLUSIONS: This study cannot conclude on ddI efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddI therapy is considered, daily doses < 750 mg should be administered.

AIDS-Related Complex↗